Barhl2 maintains T-cell factors as repressors, and thereby switches off the Wnt/β-Catenin response driving Spemann organizer formation

Sena, Elena; Rocques, Nathalie; Borday, Caroline; Amin, Harem Sabr Muhamad; Parain, Karine; Sitbon, David; Chesneau, Albert; Durand, Béatrice

doi:10.1242/dev.173112

Cited by 7 publications

(31 citation statements)

References 89 publications

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“…This interaction is independent of TCF7L1 binding to Gro/ TLE. Functional observations confirm that Barhl2 enhances the capacity of to repress transcription, and abolishes the β-catenin-driven activation of TCF/LEF target genes (Figure 1C) (Sena et al, 2019).…”

Section: Tcf/lef and Barhl2 In The Developmental Dynamics Of Spemann Organizer (So)supporting

confidence: 66%

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

Bou-Rouphael

Durand

2021

Front. Cell Dev. Biol.

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Since its first discovery in the late 90s, Wnt canonical signaling has been demonstrated to affect a large variety of neural developmental processes, including, but not limited to, embryonic axis formation, neural proliferation, fate determination, and maintenance of neural stem cells. For decades, studies have focused on the mechanisms controlling the activity of β-catenin, the sole mediator of Wnt transcriptional response. More recently, the spotlight of research is directed towards the last cascade component, the T-cell factor (TCF)/Lymphoid-Enhancer binding Factor (LEF), and more specifically, the TCF/LEF-mediated switch from transcriptional activation to repression, which in both embryonic blastomeres and mouse embryonic stem cells pushes the balance from pluri/multipotency towards differentiation. It has been long known that Groucho/Transducin-Like Enhancer of split (Gro/TLE) is the main co-repressor partner of TCF/LEF. More recently, other TCF/LEF-interacting partners have been identified, including the pro-neural BarH-Like 2 (BARHL2), which belongs to the evolutionary highly conserved family of homeodomain-containing transcription factors. This review describes the activities and regulatory modes of TCF/LEF as transcriptional repressors, with a specific focus on the functions of Barhl2 in vertebrate brain development. Specific attention is given to the transcriptional events leading to formation of the Organizer, as well as the roles and regulations of Wnt/β-catenin pathway in growth of the caudal forebrain. We present TCF/LEF activities in both embryonic and neural stem cells and discuss how alterations of this pathway could lead to tumors.

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Section: Tcf/lef and Barhl2 In The Developmental Dynamics Of Spemann Organizer (So)supporting

confidence: 66%

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

Bou-Rouphael

Durand

2021

Front. Cell Dev. Biol.

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“…However, the regulation of competence for dorsal development appears to be context dependent and may involve additional factors, including alternative TCF proteins with distinct functions after the MBT (Hamilton et al, 2001) and pathway specific repressors such as BarH like homeobox 2 (Barhl2) (Sena et al, 2019) and Xcad2 (Levy et al, 2002) that appear to function downstream of Wnt-dependent activation of sia. Barhl2, which is expressed after the loss of competence to induce dorsal Wnt target genes, stabilizes the interaction of TCF3 (also known as TCF7l1) with Gro/TLE to repress of Wnt/ß-catenin target genes in a manner that depends on Hdac1.…”

Section: Discussionmentioning

confidence: 99%

Chromatin accessibility and histone acetylation in the regulation of competence in early development

Esmaeili

Blythe²,

Tobias

et al. 2019

Preprint

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As development proceeds, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner. While key inductive signaling pathways within competent cells are well-described at a molecular level, the mechanisms by which tissues lose responsiveness to inductive signals are not well understood. Localized activation of Wnt signaling before zygotic gene activation in Xenopus laevis leads to dorsal development, but competence to induce dorsal genes in response to Wnts is lost by the late blastula stage. We hypothesize that loss of competence is mediated by changes in histone modifications leading to a loss of chromatin accessibility at the promoters of Wnt target genes. We use ATAC-seq to evaluate genome-wide changes in chromatin accessibility across several developmental stages. Based on overlap with p300 binding, we identify thousands of putative cis-regulatory elements at the gastrula stage, including sites that lose accessibility by the end of gastrulation and are enriched for pluripotency factor binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence in the early gastrula while genes involved in mesoderm and neural crest development maintain accessibility at their promoters. Inhibition of histone deacetylases increases acetylation at the promoters of dorsal Wnt target genes and extends competence for dorsal gene induction by Wnt signaling. Histone deacetylase inhibition, however, is not sufficient to extend competence for mesoderm or neural crest induction. These data suggest that chromatin state regulates the loss of competence to inductive signals in a context-dependent manner.

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“…Before stage 10, the transcription factor Barhl2 diminishes Spemann organizer fate determination 46 ; between stage 10 and stage 14, its overexpression promotes apoptosis in the Xenopus dorsal part. 16 We asked whether Barhl2 transcriptionally regulates mcl1.…”

Section: Depletion Of Barhl2 Activity Compensates For Mcl1 Depletion But Does Not Affect Apoptotic Cascade Components' Gene Expressionmentioning

confidence: 99%

“…We previously observed that Barhl2 overexpression promotes apoptosis in the Xenopus neuroectoderm, and mesoderm. 16,46 A phylogenetic analysis demonstrates that the nematode Ceh-30 is the ortholog of Barhl proteins (reviewed in References 81, 82. Three C. elegans genetic screens, performed independently, highlight the regulation of the apoptotic pathway by Barhl orthologs.…”

Section: Casp7 Is the Executioner Protease In Early Neurula Embryosmentioning

confidence: 99%

Mcl1 protein levels and Caspase‐7 executioner protease control axial organizer cells survival

Sena

Bou-Rouphael²,

Rocques

et al. 2020

Developmental Dynamics

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Background: Organizing centers are groups of specialized cells that secrete morphogens, thereby influencing development of their neighboring territories.Apoptosis is a form of programmed cell death reported to limit the size of organizers. Little is known about the identity of intracellular signals driving organizer cell death. Here we investigated in Xenopus the role of both the antiapoptotic protein Myeloid-cell-leukemia 1 (Mcl1) and the cysteine proteases Caspase-3 and Caspase-7 in formation of the axial organizing center-the notochord-that derives from the Spemann organizer, and participates in the induction and patterning of the neuroepithelium.Results: We confirm a role for apoptosis in establishing the axial organizer in early neurula. We show that the expression pattern of mcl1 is coherent with a role for this gene in early notochord development. Using loss of function approaches, we demonstrate that Mcl1 depletion decreases neuroepithelium width and increases notochord cells apoptosis, a process that relies on Caspase-7, and not on Caspase-3, activity. Our data provide evidence that Mcl1 protein levels physiologically control notochord cells' survival and that Caspase-7 is the executioner protease in this developmental process.Conclusions: Our study reveals new functions for Mcl1 and Caspase-7 in formation of the axial signalling center.

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Barhl2 maintains T-cell factors as repressors, and thereby switches off the Wnt/β-Catenin response driving Spemann organizer formation

Cited by 7 publications

References 89 publications

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development

Chromatin accessibility and histone acetylation in the regulation of competence in early development

Mcl1 protein levels and Caspase‐7 executioner protease control axial organizer cells survival

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